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High\u2010resolution structural analysis of alpha\u2010synuclein bound to small lipid or detergent micelles revealed two helices connected by a non\u2010helical linker, but corresponding studies of the vesicle\u2010bound extended\u2010helix state are hampered by the size and heterogeneity of the protein\u2010vesicle complex. Here we employ fluorinated alcohols (FAs) to induce a highly helical aggregation\u2010resistant state of alpha\u2010synuclein in solution that resembles the vesicle\u2010bound extended\u2010helix state but is amenable to characterization using high\u2010resolution solution\u2010state NMR. Analysis of chemical shift, NOE, coupling constant, PRE and relaxation measurements shows that the lipid\u2010binding domain of alpha\u2010synuclein in FA solutions indeed adopts a single continuous helix and that the ends of this helix do not come into detectable proximity to each other. The helix is well ordered in the center, but features an increase in fast internal motions suggestive of helix fraying approaching the termini. The central region of the helix exhibits slower time scale motions that likely result from flexing of the highly anisotropic structure. Importantly, weak or missing short\u2010 and intermediate\u2010range NOEs in the region corresponding to the non\u2010helical linker of micelle\u2010bound alpha\u2010synuclein indicate that the helical structure in this region of the protein is intrinsically unstable. This suggests that conversion of alpha\u2010synuclein from the extended\u2010helix to the broken\u2010helix state represents a functionally relevant structural transition.<\/jats:p>","DOI":"10.1002\/pro.3426","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T04:30:59Z","timestamp":1523939459000},"page":"1314-1324","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Structure and dynamics of the extended\u2010helix state of alpha\u2010synuclein: Intrinsic lability of the linker region"],"prefix":"10.1002","volume":"27","author":[{"given":"Yoon\u2010Hui","family":"Sung","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Program in Structural Biology Weill Cornell Medicine New York New 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